Indoles in Edible Members of the Cruciferae

Wall, Monroe E.; Taylor, H. M.; Perera, Premila; Wani, Mansukh C.

doi:10.1021/np50055a020

Cited by 22 publications

(8 citation statements)

References 9 publications

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“…I3CA was a major oxidative metabolite of I3C in plasma samples, in agreement with unpublished data in Wall et al (40). I3A was detected at very low levels in the plasma up to and including 45 min.…”

Section: Discussionsupporting

confidence: 91%

Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice

Anderton

Manson²,

Verschoyle³

et al. 2004

Clinical Cancer Research

196

172

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Indole-3-carbinol (I3C) and 3,3-diindolylmethane (DIM) are promising cancer chemopreventive agents in rodent models, but there is a paucity of data on their pharmacokinetics and tissue disposition. The disposition of I3C and its acid condensation products, DIM, [2-(indol-3-ylmethyl)-indol-3-yl]indol-3-ylmethane (LTr 1 ), indolo[3,2b]carbazole (ICZ) and 1-(3-hydroxymethyl)-indolyl-3-indolylmethane (HI-IM) was studied, after oral administration of I3C (250 mg/kg) to female CD-1 mice. Blood, liver, kidney, lung, heart, and brain were collected between 0.25 and 24 h after administration and the plasma and tissue concentrations of I3C and its derivatives determined by high-performance liquid chromotography. I3C was rapidly absorbed, distributed, and eliminated from plasma and tissues, falling below the limit of detection by 1 h. Highest concentrations of I3C were detected in the liver where levels were approximately 6-fold higher than those in the plasma. Levels of DIM, LTr 1 , and HI-IM were much lower, although they persisted in plasma and tissues for considerably longer. DIM and HI-IM were still present in the liver 24 h after I3C administration. Tissue levels of DIM and LTr 1 were found to be in equilibrium with plasma at almost every time point measured. In addition to acid condensation products of I3C, a major oxidative metabolite (indole-3-carboxylic acid) and a minor oxidative metabolite (indole-3-carboxaldehyde) were detected in plasma of mice after oral administration of I3C. ICZ was also tentatively identified in the liver of these mice. This study shows for the first time that, after oral administration to mice, I3C, in addition to its acid condensation products, is absorbed from the gut and distributed systemically into a number of well-perfused tissues, thus allowing the possibility for some pharmacological activity of the parent compound in vivo.

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Section: Discussionsupporting

confidence: 91%

Pharmacokinetics and Tissue Disposition of Indole-3-carbinol and Its Acid Condensation Products after Oral Administration to Mice

Anderton

Manson²,

Verschoyle³

et al. 2004

Clinical Cancer Research

196

172

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“…19 However, ours is the first showing that enteral administration of ICA or indole expressing microbes can provide prophylactic cytoprotective activity in GVHD while maintaining GVL responses. The lack of evident toxicity following ICA administration and its presence as a prebiotic nutraceutical in a variety of common food stuffs 14,46 support its further evaluation as a therapeutic for GVHD.…”

Section: Discussionmentioning

confidence: 99%

Indoles derived from intestinal microbiota act via type I interferon signaling to limit graft-versus-host disease

Swimm

Giver

DeFilipp

et al. 2018

Blood

143

115

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Abstract The intestinal microbiota in allogeneic bone marrow transplant (allo-BMT) recipients modulates graft-versus-host disease (GVHD), a systemic inflammatory state initiated by donor T cells that leads to colitis, a key determinant of GVHD severity. Indole or indole derivatives produced by tryptophan metabolism in the intestinal microbiota limit intestinal inflammation caused by diverse stressors, so we tested their capacity to protect against GVHD in murine major histocompatibility complex–mismatched models of allo-BMT. Indole effects were assessed by colonization of allo-BMT recipient mice with tryptophanase positive or negative strains of Escherichia coli, or, alternatively, by exogenous administration of indole-3-carboxaldehyde (ICA), an indole derivative. Treatment with ICA limited gut epithelial damage, reduced transepithelial bacterial translocation, and decreased inflammatory cytokine production, reducing GVHD pathology and GVHD mortality, but did not compromise donor T-cell-mediated graft-versus-leukemia responses. ICA treatment also led to recipient-strain-specific tolerance of engrafted T cells. Transcriptional profiling and gene ontology analysis indicated that ICA administration upregulated genes associated with the type I interferon (IFN1) response, which has been shown to protect against radiation-induced intestinal damage and reduce subsequent GVHD pathology. Accordingly, protective effects of ICA following radiation exposure were abrogated in mice lacking IFN1 signaling. Taken together, these data indicate that indole metabolites produced by the intestinal microbiota act via type I IFNs to limit intestinal inflammation and damage associated with myeloablative chemotherapy or radiation exposure and acute GVHD, but preserve antitumor responses, and may provide a therapeutic option for BMT patients at risk for GVHD.

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“…10 Glucosinolate hydrolysis often occurs during cooking of Brassica crops (such as cabbage, brussel sprouts, and cauliflower) leading to increased levels of nitriles from these sources. 11…”

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confidence: 99%